The major goal is to investigate the structure-function properties of G protein gated K+ channels of the CNS. cDNA clones coding for 5-HT1a coupled K+ channels of hippocampus and/or the Raphe nucleus will be isolated and characterized. The identity of the G proteins responsible for coupling receptor to channel will be determined. Structure-function studies by site-directed mutagenesis of both channel and G protein combined with detailed electrophysiological analyses of the kinetics and mechanism of the coupling will be used to determine the molecular nature of G protein activation of the channels.